Abstract: BACKGROUND AND AIMS: Synchronous and heterochronous multiple soft tissue sarcoma of the extremities is very rare. Out of 1,201 of our patients, 4 patients presented with symmetrical bilateral soft tissue sarcoma of the extremities. The aim of this study was to identify possible reasons for this unusual manifestation of sarcomas. MATERIALS AND METHODS: The patients' data was acquired by review of the patients' charts and follow-up information was gathered by phone calls to the patients or their relatives and their general practitioners. RESULTS: All tumours were located at the extremities and were diagnosed as leiomyosarcoma in two patients, malignant fibrous histiocytoma and clear cell sarcoma in one patient each. No other individual or family history of cumulation of neoplasms was known in the patients. The median interval between the diagnoses was 3 1/2 years (range: 4 months to 9 1/2 years). In two patients a second primary sarcoma of the same entity was considered the most likely diagnosis, whereas in one patient a contralateral lymph node metastasis and in one other patient an atypical soft tissue metastasis had to be taken into account. A positive family history with a father with malignant fibrous histiocytoma may indicate a hereditary predisposition in one patient. Aside from irradiation effects, exposition to other carcinogenic agents or genetic predisposition, the reasons for the clustering of soft tissue sarcoma in one same patient remain still unclear. Only one patient, although suffering from disseminated metastatic disease was living at follow-up time, the other three patients had already died. CONCLUSION: The interpretation of the bilateral manifestation of soft tissue sarcoma remains open, but predicts an unfavourable outcome.
Abstract: INTRODUCTION: Soft tissue sarcomas represent a heterogeneous group of tumours with a wide range of clinical behaviour. Exact determination of diagnosis and prognosis is critical in order to guide surgical decisions and provide systemic therapy or radiation for patients. The value of consultative second opinions has been proven for general surgical pathology; some studies suggest an even higher value for the soft tissue tumour specimens in particular. METHODS: We reviewed 603 patients who were operated on at our institution with the diagnosis of soft tissue sarcoma and aggressive fibromatosis; we focused on mismatches in primary and definite tumour-entity and -grading with respect to the diagnosing institution and the primary surgical procedure. RESULTS: We found concordant primary diagnosis in 28.3% for pathologists in private clinics, 29.6% for hospital pathologists, 36.8% for academic medical centres (university hospitals) and 70.5% for the Department of Pathology at our institution. An improvement in diagnosis or confirmation of the correct primary diagnosis by the second opinion was seen in 73.1% of the patients; in 2.5%, the second opinion was false. DISCUSSION: For accurate determination of prognosis and to provide optimal therapeutic decisions we consider expert second opinion essential for optimal treatment of soft tissue sarcomas.
Abstract: OBJECTIVES: The growing number of patients with impaired wound healing and the development of multidrug-resistant bacteria demand the investigation of alternatives in wound care. The antimicrobial activity of naturally occurring host defence peptides and their derivatives could be one alternative to the existing therapy options for topical treatment of wound infection. Therefore, the aim of this study was to investigate the antimicrobial activity of proline-novispirin G10 (P-novispirin G10) in vitro and in the infected porcine titanium wound chamber model. METHODS: The new derived designer host defence peptide P-novispirin G10 was tested in vitro against Gram-positive and Gram-negative bacterial strains. Additionally, cytotoxicity and haemolytic activities of P-novispirin G10 and protegrin-1 were measured. For in vivo studies, six wound chambers were implanted on each flank of Göttinger minipigs (n = 2, female, 6 months old, 15-20 kg). Eleven wound chambers were inoculated 8 days post-operatively with 5 x 10(8) of Staphylococcus aureus; one wound chamber remained uninfected as a system control. After wound infection had been established (4 days after inoculation), each wound chamber was topically treated with P-novispirin G10, protegrin-1 or carrier control. Wound fluid was harvested every hour for a total follow up of 3 h. RESULTS: P-novispirin G10 demonstrated broad-spectrum antimicrobial activity with moderate haemolytic and cytotoxic activities compared with protegrin-1. In the infected wound chamber model P-novispirin G10 demonstrated a 4 log(10) reduction in bacterial counts. CONCLUSIONS: This implicates the potential of P-novispirin G10 as an alternative in future antimicrobial wound care. However, more studies are necessary to further define clinical applications and potential side effects in greater detail.
Abstract: BACKGROUND: Elastofibromas are benign soft tissue tumours mostly of the infrascapular region between the thoracic wall, the serratus anterior and the latissimus dorsi muscle with a prevalence of up to 24% in the elderly. The pathogenesis of the lesion is still unclear, but repetitive microtrauma by friction between the scapula and the thoracic wall may cause the reactive hyperproliferation of fibroelastic tissue. METHODS: We present a series of seven cases with elastofibroma dorsi with reference to clinical findings, further clinical course and functional results after resection, as well as recurrence. Data were obtained retrospectively by clinical examination, phone calls to the patients' general practitioners and charts review. Follow-up time ranged from four months to nine years and averaged 53 months. RESULTS: The patients presented with swelling of the infrascapular region or snapping scapula. In three cases, the lesion was painful. The ratio men/women was 2/5 with a mean age of 64 years. The tumor sizes ranged from 3 to 13 cm. The typical macroscopic aspect was characterized as poorly defined fibroelastic soft tissue lesion with a white and yellow cut surface caused by intermingled remnants of fatty tissue. Microscopically, the lesions consisted of broad collagenous strands and densely packed enlarged and fragmented elastic fibres with mostly round shapes. In all patients but one, postoperative seroma (which had to be punctuated) occurred after resection; however, at follow-up time, no patient reported any decrease of function or sensation at the shoulder or the arm of the operated side. None of the patients experienced a relapse. CONCLUSION: In differential diagnosis of soft tissue tumors located at this specific site, elastofibroma should be considered as likely diagnosis. Due to its benign behaviour, the tumor should be resected only in symptomatic patients.
Abstract: Cystic necrotization with liquefaction and calcification of muscle tissue is a rare late sequel of compartmental syndrome. Diagnosis and treatment of this clinical picture is still a problem. In the literature, various therapeutic approaches are described such as incision, needle decompression, and complete compartmental debridement. We report a case in which cystic degradation and liquefaction of three compartments developed 51 years after a complete fracture of the tibia. The patient was treated by radical compartmental resection. No postoperative complication was noted, and almost no functional loss occurred.
Abstract: Acral manifestations of systemic sclerosis include Raynaud's phenomenon, calcinosis cutis, and sclerodactyly. In the later stages of the disease, contractures of the skin and joints as well as obliterative vasculopathy leading to digital ulcers and necrotic lesions may occur. Patients with acral manifestations of systemic sclerosis are ideally treated by a team that includes a rheumatologist, dermatologist, hand surgeon, physiotherapist, and, eventually, a psychologist. Calcium channel antagonists, alpha(1)-adrenergic blockade with prazosin, and prostacyclin analogs were proven to be effective in the treatment of scleroderma-related Raynaud's phenomenon. Losartan, an angiotensin II receptor inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor, have been beneficial for systemic sclerosis-associated Raynaud's phenomenon in pilot studies. Parenteral prostacyclin analogs, e. g., iloprost, can be recommended as first-line treatment of ischemic digital ulcers. When prostacyclin analogs fail, the phosphodiesterase type 5 inhibitor sildenafil can be tried to improve ulcer healing. Bosentan, an endothelin receptor antagonist, may prevent new digital ulcers. At present, there are no medical agents agreed to be generally effective in the reduction of calcinotic deposits or cutaneous fibrosis, although some drugs have been identified as potentially beneficial. Surgical treatment of acral manifestations consists of excision or curettage of symptomatic calcific deposits, digital sympathectomy, arterial reconstruction, and amputation in rare cases. Flexion contractures of the proximal interphalangeal joints, with secondary hyperextension of the metacarpophalangeal joints, can be treated by arthrodesis of the proximal interphalangeal joints and resection arthroplasty or prostheses at the metacarpophalangeal joints to improve hand function.
Abstract: Despite new techniques and better health programs in western industrialized nations, the numbers of amputations on the lower extremity remain constant. Approximately 100,000 amputations are performed annually in the U.S. and about 10,000 in Germany, more than 90% for gangrene resulting from ischemia and/or infection. Micro- and macroangiopathic changes in diabetes are the major cause of ischemia in the leg. The preservation of limb length and construction of an end bearing stump are important criteria for the functional outcome after amputation. Especially in trauma and tumor patients with "planned" amputations, all effort should be made to achieve an end bearing stump with sufficient length respectively an amputation level that is suitable for orthosis instead of prosthetic supplementation. After amputation, an interdisciplinary approach is mandatory to achieve sufficient soft tissue coverage or stump distalization. In case of insufficient bearing ability of the stump, various reconstructive possibilities must be considered to assure optimal outcome.
Abstract: Clinical manifestations of scleroderma at the hand include Raynaud's phenomenon, calcinosis cutis, sclerodactylia and teleangiectasia. With the progression of the disease, cutaneous and joint contractions, acro-osteolysis, necrosis of the finger tips, and even extensive digital ulceration are likely to occur. These painful and often rapidly advancing lesions cause loss of function and disfigurement and, untreated, often lead to mutilation of the affected hand. Only an interdisciplinary management including the hand surgeon, the rheumatologist, and the physiotherapist can guarantee optimal treatment. Drug therapy should be included as well as physical therapy. Both should be made use of before and accompanying surgical treatment. Surgical therapy consists of treatment of the infections, excision of calcinosis, arthrodesis, in particular of the proximal interphalangeal joints, and sympathectomy. Amputation remains a final option, whereas with timely and sufficient treatment, amputations can be avoided and an improvement of function and an alleviation of the symptoms can be achieved. Among the non-operative treatment options, behavioural training, calcium antagonists, prostacyclin derivatives, topical nitrates as well as plexus anesthesia and stellatum blocks have proved to be effective. Recent drug therapies include endothelin-receptor antagonists for the prevention of digital ulceration and phosphodiesterase-V antagonists in treatment of Raynaud's phenomenon and induction of ulcer healing. With reference to several cases seen at our institution, we propose an interdisciplinary treatment concept for acral manifestations of scleroderma.
Abstract: Skin is a substantial immune organ and represents the most important barrier against the potentially hostile environment. Its first line of defense are effector molecules of the innate immune system, which in contrast to the adaptive immune system reacts immediately against penetrating pathogenic microbes. Antimicrobial peptides represent the basis of the phylogenetically oldest part of the immune system. New studies show that reduced local cutaneous expression of antimicrobial peptide in burned skin is involved in the higher incidence of wound infections. The epithelium has an essential function in recognizing colonies of micro-organisms and in initial antimicrobial defenses.
Abstract: INTRODUCTION: Bacterial infections represent a large proportion of emergencies in hand surgery. In some cases, pyoderma gangrenosum and mycobacterial infection may present with the same symptoms of swelling, pain, and purulent secretion. In these cases, operative treatment would be harmful. Therefore two cases-pyoderma gangrenosum and tuberculosis-are presented here in relation to common bacterial hand infection. METHODS: Using two case reports of diseases that only rarely affect the hands, their relevance to differential diagnosis is shown with reference to the literature. RESULTS: In both cases, we found clinical symptoms of bacterial hand infection with negative bacterial smear tests. After several debridements, pyoderma gangrenosum of the dorsum of the hand was diagnosed in one patient after pyodermiform lesions at the thigh and the nasal septum were detected and pre-existing colitis ulcerosa was taken into consideration. Corticoid therapy induced complete remission. The second patient with similar clinical symptoms had been operated on at another hospital several times before being transferred to our institution. The presumptive diagnosis of pyoderma gangrenosum was made, and under treatment with prednisone the symptoms quickly improved. After 2 weeks, the wound conditions and the patient's condition rapidly worsened. Following amputation at the upper arm level, the patient died of septic multiple organ failure. Autopsy studies revealed tuberculous sepsis originating from the hand. DISCUSSION: Patient history should be evaluated carefully because of its value to correct diagnosis. In case of negative smear tests, especially from immunocompromised, elderly patients and in patients with a history of pulmonary tuberculosis, Ziehl-Neelsen staining should be obtained. In case of multilocular affection or pre-existing chronic inflammatory bowel disease, the presumptive diagnosis of pyoderma gangrenosum can be confirmed by biopsies from the lesions margin. In both cases, unnecessary traumatizing operations could thus be avoided and treatment optimized.
Abstract: BACKGROUND: The hostile environment found in acute and chronic wounds decreases the physiological half-life of purified synthetic or recombinant peptides dramatically. Gene therapy, on the other hand, may be a viable option since it relies on the cellular machinery of the host to locally manufacture the proteins of interest. The aim of this study was to evaluate and optimize the local administration of transient cutaneous adenoviral gene delivery in wounds. METHODS: Primary human keratinocytes (HKC) and HaCaT cells were transfected with replication-deficient adenovirus (Ad5) containing the reporter gene for beta-galactosidase (LacZ). The vector was used alone or precoated with either (1) Lipofectamine 2000, (2) FuGENE 6, or (3) Polybrene. For in vivo testing a rat burn model was used. Animals were randomized into three groups: (1) Ad5-LacZ alone; (2) Ad5-LacZ precoated with Polybrene, or (3) carrier control (phosphate-buffered saline (PBS)). Samples were harvested from burned and unburned tissue sections after either 48 h or 7 days. Transgene expression was quantified by bioluminometric assay and localized using immunohistochemistry. A BrdU assay was performed to determine the influence of the used transfection reagents on cell proliferation. RESULTS: Transfection efficacy was significantly improved in vitro (p < 0.001) as well as in partial thickness burned (p = 0.015) and unburned skin (p > 0.001) after precoating Ad5 with Polybrene compared to Ad5 alone. Transgene expression was 10-fold higher in burned skin (9305 pg/mg protein) compared to unburned skin (859 pg/mg protein). CONCLUSIONS: It is feasible to improve transfection efficacy in vitro and in vivo by precoating the adenovirus with Polybrene.
Abstract: BACKGROUND: Solitary fibrous tumors (SFT) represent a rare entity of soft tissue tumors. Previously considered being of serosal origin and solely limited to the pleural cavity the tumor has been described in other locations, most particularly the head and neck. Extrathoracic SFT in the soft tissues of the trunk and the extremities are very rare. Nine cases of this rare tumor entity are described in the course of this article with respect to clinicopathological data, follow-up and treatment results. METHODS: Data were obtained from patients' records, phone calls to the patients' general practitioners, and clinical follow-up examination, including chest X-ray, abdominal ultrasound, and MRI or computed tomography. RESULTS: There were 6 females and 3 males, whose age at time of diagnosis ranged from 32 to 92 years (mean: 62.2 years). The documented tumors' size was 4.5 to 10 cm (mean: 7 cm). All tumors were located in deep soft tissues, 3 of them epifascial, 2 subfascial, 4 intramuscular. Four tumors were found at the extremities, one each at the flank, in the neck, at the shoulder, in the gluteal region, and in the deep groin. Two out of 9 cases were diagnosed as atypical or malignant variant of ESFT. Complete resection was performed in all cases. Follow-up time ranged from 1 to 71 months. One of the above.mentioned patients with atypical ESFT suffered from local relapse and metastatic disease; the remaining 8 patients were free of disease. CONCLUSION: ESFT usually behave as benign soft tissue tumors, although malignant variants with more aggressive local behaviour (local relapse) and metastasis may occur. The risk of local recurrence and metastasis correlates to tumor size and histological status of surgical resection margins and may reach up to 10% even in so-called "benign" tumors. Tumor specimens should be evaluated by experienced soft tissue pathologists. The treatment of choice is complete resection followed by extended follow-up surveillance.
Abstract: The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determined up to 30 days. Expression was quantified by FACS analysis and fluorimeter. Cytotoxicity was measured using the trypan blue exclusion method. 45 male Sprague Dawley rats received 2x10(8) pfu of Ad5-CMV-LacZ or carrier control intradermally into either superficial partial thickness scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days posttreatment. Transgene expression was assessed using immunohistochemistry and bioluminescent assays. The highest transfection rate was observed 48 h posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP expression was detectable in all groups over 30 days (P>0.05). Cytotoxic effects of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30 days. Reporter gene expression in vivo was significantly higher in burned skin compared with unburned skin (P=0,004). Gene expression decreases from 2 to 7 days with no significant expression after 14 days. This study demonstrates that effective adenoviral-mediated gene transfer of epidermal primary cells and cell-lines is feasible. Ex vivo gene transfer in epithelial cells might have promise for the use in severely burned patients who receive autologous keratinocyte sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors causes significant concentrations in the wound tissue for at least 1 week. Based on these findings, we hypothesize that transient cutaneous adenoviral gene delivery of wound healing promoting factors has potential for clinical application.
Abstract: The adenomatous polyposis coli (APC) protein is a key component of the WNT signalling pathway wherein it acts as a scaffolding protein in controlling the level of the proto-oncoprotein beta-catenin. Although APC has been shown to be genetically or epigenetically inactivated in a variety of carcinomas, little is known about its role in sarcoma. Liposarcomas (LPSs) are the second most common soft tissue sarcoma in adults. Despite different histology and malignancy, the myxoid and round-cell LPSs belong to one tumour entity characterized by a specific chromosomal translocation. We assessed the extent of genetic and epigenetic inactivation of the APC gene in myxoid/round-cell LPS. Sequencing of the mutation cluster region, the protein truncation test and a loss of heterozygosity (LOH) analysis did not reveal any genetic alterations of the APC gene in all of the liposarcoma samples. Methylation of the APC promoter was detected by methylation-specific PCR in 9 of 20 (45%) tumours. Analysis of APC expression by semiquantitative RT-PCR in a subset of the samples demonstrated that tumours with a methylated APC promoter showed a downregulation of the APC transcript. However, APC downregulation was not correlated with a stabilisation of the beta-catenin protein. Thus, the epigenetic regulation of the APC gene might play an important role in the pathogenesis of myxoid/round-cell LPS. However, the impact of APC methylation on liposarcoma development is quite likely not mediated through WNT signalling.
Abstract: Background. Transfection efficacy after nonviral gene transfer in primary epithelial cells is limited. The aim of this study was to compare transfection efficacy of the recently available method of nucleofection with the established transfection reagent FuGENE6. Methods. Primary human keratinocytes (HKC), primary human fibroblasts (HFB), and a human keratinocyte cell line (HaCaT) were transfected with reporter gene construct by FuGENE6 or Amaxa Nucleofector device. At corresponding time points, beta-galactosidase expression, cell proliferation (MTT-Test), transduction efficiency (X-gal staining), cell morphology, and cytotoxicity (CASY) were determined. Results. Transgene expression after nucleofection was significantly higher in HKC and HFB and detected earlier (3 h vs. 24 h) than in FuGENE6. After lipofection 80%-90% of the cells remained proliferative without any influence on cell morphology. In contrast, nucleofection led to a decrease in keratinocyte cell size, with only 20%-42% proliferative cells. Conclusion. Related to the method-dependent increase of cytotoxicity, transgene expression after nucleofection was earlier and higher than after lipofection.
Abstract: Reconstructive surgery of detached extremities, especially fingers, has a long historical tradition. The first clinically correctly documented cases go back to the 19th century. During the first and second world wars numerous reports appeared about the surgical care of war victims. Pioneering innovative surgical methods were developed by especially motivated surgeons for the reconstruction of these disfiguring war injuries in Europe. Because of these particular circumstances and the prevailing revolutionary spirit, many innovations in surgery were developed. The report of Otto Hilgenfeldt (1950) described his unusual approach in reconstructing a finger by using the great toe.
Abstract: In the face of emerging multidrug-resistant microbes, reliable animal models are needed to study potential new therapies in infected wounds. To this end, we implanted screw-top titanium chambers subdermally in full-thickness wounds on both flanks (n = 6 per flank) of 2 Goettinger minipigs. After 1 wk, chambers were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, or vehicle only. Throughout the study, wound fluid was harvested for quantitative bacterial cultures to monitor infection. Animals were followed for 4 wk, after which tissue biopsies were taken for histologic analysis and quantitative bacterial counts. The implanted titanium chambers were well tolerated by the pigs throughout the study. After inoculation of the chambers, wound infection was established and maintained for 14 d. Despite infection, no systemic effects were noted. Cross-contamination was negligible, compared with the vehicle-only control. After tissue ingrowth, each chamber creates a closed system that allows harvest of exudate or application of substances without loss of material from the chamber. Because 12 chambers are implanted in each pig, researchers have the opportunity to compare multiple treatment options (for example, antibiotics, antimicrobial peptides, gene therapy) in the same animal, with no interindividual variation. We conclude that the use of titanium chambers in pigs provides a reliable and reproducible in vivo model to investigate wound healing, wound infection, and treatment options.
Abstract: OBJECTIVES: Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity. METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria. RESULTS: Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control. CONCLUSIONS: These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.
Abstract: INTRODUCTION: It is well known that in patients suffering from major burn injuries of more than 15% of total body surface area (TBSA), capillary leak and loss of proteins including immunoglobulins (Ig) lead to cardiovascular failure and significantly elevated risk of infections. However, knowledge of the resulting protein profiles is limited. In order to elucidate quantitative and qualitative protein loss in human burn wounds we compared wound fluid (WF) protein content with serum protein levels. MATERIAL AND METHODS: Eleven patients suffering from second degree burns of 18-68% TBSA were enrolled in the study. Immediately after admission burn wounds were enclosed in cutaneous vinyl wound chambers covering a 2.25 cm(2) wound surface area. WF and serum samples were harvested every 8 h with a follow up of 48 h and analyzed for total protein content, albumin and the immunoglobulins A, E, G and M. RESULTS: Protein levels in serum were significantly lower as compared to physiological levels while WF protein levels were elevated and remained high. Total protein (TP) and albumin (AL) accumulated in high concentrations on the wound surface (average accumulation on 10% burnt TBSA within 8 h: TP=16.59+/-8.86 g; AL=12.39+/-5.87 g). The albumin fraction in WF showed increasing values (24 h: 69%; 32 h: 86%) although the serum albumin fraction remained nearly unchanged (55%). Peak values were initially found for all immunoglobulins both in serum and WF. IgA, E and M reached a steady state 32 h post-trauma, whereas IgG continuously decreased until 40 h. IgG values in serum were significantly below physiological levels at all time points. CONCLUSIONS: This study qualifies and quantifies a significant protein loss in second degree burn wounds. Protein concentrations in wound fluid correlate highly with serum concentrations until 48 h post-burn. A patient's entire amount of serum proteins accumulates in wound fluid in a 20% TBSA burn within approximately 24h. In contrast to capillary leak theory proteins and immunoglobulins extravasate to wound fluid even after 48 h post-trauma.
Abstract: Changes in hematopoiesis that occur in humans after a burn injury may have important effects on morbidity and mortality. In patients with a variety of severe diseases, the presence of erythroblasts in peripheral blood is known to be indicative of a poor prognosis. However, the prognostic significance of erythroblasts in peripheral blood of burn patients has not yet been estimated. This study included 464 consecutive burn patients, of whom 81 did not survive their injuries (17.5 percent). Together with erythroblasts in blood, data on age, sex, total burn surface area, third-degree burn, inhalation trauma, white blood cell count, C-reactive protein, and hemoglobin were studied. The mortality rate of patients with erythroblasts in peripheral blood (n = 53) amounted to 56.6 percent (n = 30; total burn surface area, 39 percent), which is significantly higher (p < 0.001) than the mortality rate of patients without erythroblasts (12.4 percent, n = 51; total burn surface area, 18.69 percent). None of the 10 patients with more than 1000 erythroblasts x 10/liter survived. The detection of erythroblasts in the peripheral blood of burn patients is highly predictive of death, with the odds ratio after adjustment for the other known prognostic factors being 8.3 (95 percent confidence interval, 4.5 to 15.3). Erythroblasts were detected for the first time on average 10 +/- 4 days (median, 6 days) after admission and 13 +/- 6 days (median, 7 days) before death. Detection of erythroblasts in burn patients is of high prognostic power with regard to in-hospital mortality, providing physicians with a strong prognostic method with which to identify seriously threatened patients. It seems attractive to think about an incorporation of erythroblasts into further refinements of burn scores.
Abstract: BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.
Abstract: BACKGROUND: The antibacterial activity of host defense peptides (HDP) is largely mediated by permeabilization of bacterial membranes. The lipid membrane of enveloped viruses might also be a target of antimicrobial peptides. Therefore, we screened a panel of naturally occurring HDPs representing different classes for inhibition of early, Env-independent steps in the HIV replication cycle. A lentiviral vector-based screening assay was used to determine the inhibitory effect of HDPs on early steps in the replication cycle and on cell metabolism. RESULTS: Human LL37 and porcine Protegrin-1 specifically reduced lentiviral vector infectivity, whereas the reduction of luciferase activities observed at high concentrations of the other HDPs is primarily due to modulation of cellular activity and/ or cytotoxicity rather than antiviral activity. A retroviral vector was inhibited by LL37 and Protegrin-1 to similar extent, while no specific inhibition of adenoviral vector mediated gene transfer was observed. Specific inhibitory effects of Protegrin-1 were confirmed for wild type HIV-1. CONCLUSION: Although Protegrin-1 apparently inhibits an early step in the HIV-replication cycle, cytotoxic effects might limit its use as an antiviral agent unless the specificity for the virus can be improved.
Abstract: The presence of erythroblasts is an accurate predictor of a poor prognosis. This study investigates whether this should be taken into account when assessing patients with burn injuries as traditional protocols may underestimate the level of risk.
Abstract: BACKGROUND: Despite dramatic improvements in the management of burns, infection still remains a serious risk for the burn patient. The aim of this study was to shed light on the impact of acute burn injury with or without infection on cytokine profiles. METHODS: Sprague-Dawley rats (n = 21) were randomized into three groups: 1) burn only 2) burn and infection or 3) sham burn. Weight was monitored and blood was collected for cytokine ELISA, LPS quantification, and peripheral blood analysis. Animals were sacrificed either after 6 or 12 days. RESULTS: Infected animals showed substantial weight loss until day 6 post-burn as compared to burn alone. Endotoxin and TNF-alpha levels were elevated early in the infected burn group within 48 hours post-burn. In contrast, significant up-regulation of the anti-inflammatory cytokine IL-10 occurred later in the clinical course and was associated with the recovery from weight loss. CONCLUSION: Our results suggest that in the presence of infection, you get a SIRS response possibly due to transient endotoxemia that is only seen in the infection group. In contrast, both burn and infection get a late IL-10 (CARS) response, which is then associated with a return to normal weight in the infection group.
Abstract: The parenteral drug application is a routinely used method in all medical disciplines. Intramuscular, intraarticular, intravenous injections and infusions can cause local complications such as abscesses, articular infections or paravasates. These local complications can lead to bacteraemia, sepsis and may lead to multiple organ failure associated with high morbidity and mortality. Although these complications are rare, they are sometimes disastrous and result in life threatening clinical conditions. During a retrospective analysis (review period 1998-2002) 24 patients were admitted and hospitalized in our department. Within this report we demonstrate 7 patients with fatal complications after injections. In the majority of cases minor patients' complaints were proceeding before major complications were present. A long and expensive treatment period with multiple surgical interventions ends up in functional disabilities and unsatisfactory aesthetic results. Instead of delayed surgical treatment immediate radical surgical care is crucial to prevent disastrous complications. In case of the inability of sufficient debridement, amputations are sometimes indicated in the sense of "life before limb". Besides the consequences for the patient these disastrous complications have a high socioeconomic impact and result in reduced reimbursement for the hospital stay.
Abstract: BACKGROUND: Because of the high resistance rate of fibrosarcomas against cytotoxic agents clinical chemotherapy of these tumors is not established. A better understanding of the diverse modes of tumor cell death following cytotoxic therapies will provide a molecular basis for new chemotherapeutic strategies. In this study we elucidated the response of a fibrosarcoma cell line to clinically used cytostatic agents on the level of gene expression. METHODS: HT1080 fibrosarcoma cells were exposed to the chemotherapeutic agents doxorubicin, actinomycin D or vincristine. Total RNA was isolated and the gene expression patterns were analyzed by microarray analysis. Expression levels for 46 selected candidate genes were validated by quantitative real-time PCR. RESULTS: The analysis of the microarray data resulted in 3.309 (actinomycin D), 1.019 (doxorubicin) and 134 (vincristine) probesets that showed significant expression changes. For the RNA synthesis blocker actinomycin D, 99.4% of all differentially expressed probesets were under-represented. In comparison, probesets down-regulated by doxorubicin comprised only 37.4% of all genes effected by this agent. Closer analysis of the differentially regulated genes revealed that doxorubicin induced cell death of HT1080 fibrosarcoma cells mainly by regulating the abundance of factors mediating the mitochondrial (intrinsic) apoptosis pathway. Furthermore doxorubicin influences other pathways and crosstalk to other pathways (including to the death receptor pathway) at multiple levels. We found increased levels of cytochrome c, APAF-1 and members of the STAT-family (STAT1, STAT3), while Bcl-2 expression was decreased. Caspase-1, -3, -6, -8, and -9 were increased indicating that these proteases are key factors in the execution of doxorubicin mediated apoptosis. CONCLUSION: This study demonstrates that chemotherapy regulates the expression of apoptosis-related factors in fibrosarcoma cells. The number and the specific pattern of the genes depend on the used cytotoxic drug. The response rates on the gene expression level, i.e. the number of genes regulated by the drugs actinomycin D, doxorubicin and vincristine, correlate to the clinical effectiveness of the drugs. Doxorubicin seems to exert its cytotoxic mechanism by regulating genes, which are involved in several different apoptosis regulating pathways. The exact knowledge of the genes affected by the drugs will help to understand the diverse modes of soft tissue sarcoma cell death in response to cytotoxic therapies.
Abstract: OBJECTIVE: The transpalpebral resection of the corrugator and depressor supercilii muscles is a new treatment option for migraine headaches. Hyperactive contractility of these muscles can provoke the peripheral compression of the supratrochlear nerve and induce a neurogenic inflammation triggering the symptoms of migraine. In order to gather detailed knowledge of the respective anatomy in the eyebrow region, a macroscopic cadaver study was conducted. MATERIALS AND METHODS: The relevant muscles of the forehead, glabella and eyebrow were dissected in five fresh, non-preserved heads. The supracanthal origins and dermal points of insertion were marked. Following the preparation of the neurovascular structures, the muscles were measured and weighed. The course of the supraorbital and supratrochlear nerves was demonstrated from the forehead to the orbital cavity. RESULTS: There are three, paired groups of muscles in the superomedial region of the orbital rim. They can be divided into the superficial frontalis and procerus muscle, the orbicularis muscle in a middle layer and the corrugator and depressor supercilii in a deeper layer. The corrugator measured approximately 4.5 cm, whose origin is superior and posterior to the depressor origin situated cranial to the medial canthus. The corrugator inserts lateral to the exit of the supraorbital nerve in the dermis above the eyebrow after penetrating the orbicularis and frontalis muscles and a subgaleal fat pad. The length and weight of the muscles is highly variable. The muscle is penetrated by the supratrochlear nerve whereas the supraorbital nerve runs underneath it. The corrugator is innervated medially and laterally by branches of the facial nerve. CONCLUSION: A detailed knowledge of the complex arrangement of the muscles acting upon the glabella and the different communicating subgaleal and preseptal fat pads allow the identification and resection of the corrugator and depressor muscles without damaging the supratrochlear nerve. The course of the specific nerves is variable. The double-innervation of the corrugator suggests its complete resection instead of the selective denervation of the muscle.
Abstract: An unusual variant of dedifferentiated liposarcoma with extensive lymphocytic component is described. A 71-year-old patient suffered from a relapse of an atypical lipomatous tumor/well-differentiated liposarcoma with early micronodular (low-grade) dedifferentiation, which had been resected 4 years before. The relapse revealed features of a dedifferentiated liposarcoma with spindle-cell, partly pleomorphic dedifferentiation and osseous metaplasia. Clearly separated from the spindle-cell areas, an extensive homogeneously dense lymphoid (lymphocytic) tumor-component was evident, with relative abrupt transition to the well-differentiated liposarcoma component. Using immunohistochemistry and PCR, the lymphoid ("lymphoma-like") infiltrate proved to be a polyclonal lymphocytic proliferation. Fluorescence in situ hybridization (FISII) analysis revealed no signs of MDM2- and CDK4-gene amplification in the lymphoid areas, although within this mononuclear lymphoid population, large polymorphic nuclei displayed an amplified number of MDM2/CDK4 gene copies, indicating the presence of truly dedifferentiated tumor cells within the lymphoid component. The results favor a reactive lymphocytic infiltration versus a neoplastic one, which might be caused for example by chemoattractive agents. An extensive lymphoid "overgrowth" must be considered within the spectrum of unusual variants and in the differential diagnosis of dedifferentiated liposarcoma.
Abstract: Host defense peptides (HDP) are naturally occurring effector molecules of the innate immune system, which might be an alternative to currently used antibiotics. The objective of this study was to investigate the efficiency of transient cutaneous adenoviral transfection with human cathelicidin hCAP-18/LL-37 in infected burn wounds. Specific transgene expression was analyzed in vitro on mRNA and protein level using real-time PCR and Western-blot. Male Sprague-Dawley rats (n=40) received a second degree scald burn on both flanks (5% BSA), which were inoculated with 10(8) colony-forming units (CFU) Pseudomonas aeruginosa. Two days later, rats were randomized into the following groups: (1) adenoviral delivery of LL-37 (Ad5-hCAP-18, n=10), (2) synthetic host defense peptide LL-37 (1 mg; n=10), (3) carrier control (PBS, n=10) and (4) empty-virus control (Ad5-LacZ, n=10). Agents were injected intradermally and subcutaneously into both flanks. After either 2 or 7 days, skin samples were harvested and homogenized. CFU per gram tissue were determined. The hCAP-18/LL-37 expression was confirmed by real-time PCR and localized using in situ hybridization. In vitro transfection of cutaneous cells delivered a specific response on mRNA production. Western blot analysis revealed protein expression of hCAP-18/LL-37 in conditioned medium and cell pellet. The host defense peptide LL-37 was detectable after cleavage of the inactive pro-form hCAP-18/LL-37 with human elastase. Ad5-hCAP-18 showed a significant bacterial inhibition of approximately 10 000 fold compared to the control group (P<0.001) and 1000-fold (P<0.001) compared to the synthetic HDP LL-37 7 post-transfection. No inhibition was observed for the carrier or empty-virus control. Real-time PCR and in situ hybridization confirmed expression of hCAP-18/LL-37. In conclusion, transient cutaneous adenoviral delivery of the host defense peptide hCAP-18/LL-37 is significantly more effective than administration of synthetic host defense peptides and might be a potential adjunct for wound treatment in the near future.
Abstract: BACKGROUND: Among the heterogeneous group of adult soft tissue sarcomas, liposarcomas represent the largest entity along with malignant fibrous histiocytomas (MFH). PATIENTS AND METHODS: This article summarizes the results of pathomorphological data on 209 liposarcomas resected over a 10-year period. RESULTS: The most common tumor site was the thigh, and the peak age incidence was in the 5th and 6th decades. In general, three major subtypes of liposarcoma can be distinguished in terms of pathomorphology: well-differentiated/dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Well-differentiated liposarcomas represent malignancy grade 1 tumors without biological potential to metastasize, but which are able to relapse locally in cases of incomplete resection. When a local relapse has occurred, the liposarcoma may show dedifferentiation and may metastasize. CONCLUSIONS: In the pathologic-anatomical diagnosis of liposarcomas, conventional light-microscopic findings are decisive. Additional methods of molecular pathology may help in single cases to gain further insights.
Abstract: In cases of extended post-traumatic soft-tissue and bone loss as well as with mutilating infection or radical tumor resection, multidisciplinary options are required to salvage extremities and functional rehabilitation. A surgical team approach allows for reduction of amputation rates, wound healing complications, and secondary procedures in limb oncology and trauma. The goals and limitations of cooperative surgical concepts are described. In the future, continuing medical education will focus not only on indications and techniques but also on complication management, medicolegal problems, and economic deficits due to maladapted legal structures. Provided clear clinical pathways are introduced to guide indications, surgical procedures, and postoperative treatment, marked financial deficits may be avoided. While, in the past, responsibility for the patient and ethical considerations resulted in the development of voluntary interdisciplinary treatment programs, economic strategies and an increasing number of malpractice suits will inevitably produce new imperatives for interdisciplinary cooperation in the future.
Abstract: Liposarcoma is the second most common malignant soft-tissue tumor in adults. Between 1991 and 2002, 167 patients with extremity liposarcomas were treated in our center. Fifty tumors were classified as G1 liposarcomas (30%), 76 as G2 liposarcomas (45.5%), and 41 as G3 liposarcomas (24.5%). In 158 patients, (93.5%) wide tumor excision was performed. Major amputation was necessary in five patients. After a median follow-up of 36 months, 37 patients had developed local recurrence. The 5-year overall survival rate was 79%. The 5-year survival rate in primary tumors was 71/79 (90%, P<0.05) whereas 61/88 of recurrences relapsed locally (69%, P<0.05). Multidisciplinary cooperation in a tumor board is a precondition for adequate treatment.
Abstract: The development of Fournier's gangrene after Milligan-Morgan hemorrhoidectomy of a previously healthy 76-year-old female patient is described. After such a common surgical procedure, the patient developed full-thickness skin necrosis of the perianal region including the rectum. Immediate radical debridement was mandatory. Because of rectal involvement, a diverting sigmoid colostomy was required. The rectum had to be removed by abdominoperineal resection. This disastrous complication was completely unexpected and unpredictable after Milligan-Morgan hemorrhoidectomy because of the lack of predisposing factors.
Abstract: Gorham-Stout disease is a rare idiopathic syndrome with distinctive clinical, pathologic and radiologic features. It is a variant form of osseus angiomatosis associated with massive osteolysis of bone. Usually appearing after trauma, the disease is described to occur at any age. Especially in case of thoracic involvement (chylothorax), lethal outcomes are reported. In Medline, about 200 cases have been described. A patient with osteolysis of the right hand following contusion at the age of two years is reported. Despite radiotherapy and repeated bone grafting, the osteolysis progressed until today (24 years). The pathologic features and various treatment methods for hand involvement are discussed.
Abstract: Morphological findings of 21 soft tissue sarcomas of adulthood following preoperative chemo- and/or radiotherapy including perfusion therapy and resection are presented. The therapy-induced changes included a spectrum ranging from total tumor regression up to still completely vital tumor (median of all cases: 30% vital tumor tissue). 7 of 21 sarcomas (33%) were evaluated as responders (grade I-III). So-called malignant fibrous histiocytoma (MFH) revealed a good tumor response to preoperatively administered therapy (regression grades I and II). Myxoid/round-cell liposarcoma exhibited regression grades of IV-V (i.e. 30% up to 95% vital tumor tissue, non-responders). Synovial sarcoma was characterized by regression grades III up to VI (i.e. up to 100% vital tumor tissue without any signs of regression, 83% non-responders). Completely vital tumor was evident in 2 synovial sarcomas despite preoperative tumor therapy. These findings hint towards differences in response of distinct sarcoma entities to preoperative chemo-/radiotherapy. A grading of therapy-induced tumor regression in adult soft tissue sarcomas may best refer to already established grading schemes (e.g. according to the grading scheme for osteosarcomas following chemotherapy of Salzer-Kuntschik). A report of sarcoma resection specimens should include the percentage of vital tumor tissue.
Abstract: Subcutaneous liposuction in tumescent technique is the most frequent aesthetic plastic procedure in the United States. In Germany, nearly 250,000 liposuctions are done per year by a variety of surgical and nonsurgical specialists including plastic surgeons, dermatologists, gynecologists, oral surgeons, and otolaryngologists in settings ranging from hospital operating rooms to physicians' offices. The method is applied and promoted as an easy-to-learn technique that is suited as an outpatient procedure. Although major complications seem to be rare, there are definite risks, including death at a rate of 1/5,000 procedures. Major risk factors are insufficient hygiene standards, multiliter wetting solution infiltration, megavolume aspiration, multiple cosmetic procedures in one setting, sedative and anesthetic drug hangover threatening ventilation, permissive postoperative discharge, and mistakes in patient selection. When major complications occur, office-based practitioners may refer patients to hospital emergency departments, where medical personnel unfamiliar with this procedure may underestimate the risk of major complications.
Abstract: A 45-year-old orthopaedic surgeon sustained a complete thumb amputation and severe injuries to his index finger in a lawn mower accident. He was treated with a combined second toe transfer and an index finger pollicization.
Abstract: 5% of all multiple myelomas manifest as solitary plasmocytomas. The multiple myeloma is the most frequent malignant transformation of the haematopoetic system, with an incidence of 2:100,000 per year. 1% of all solitary plasmocytomas are found in the extremities, accounting for less than one case per year in Germany. In this article we present the case of a fifty year old patient with a solitary plasmocytoma of the shoulder region and discuss the diagnostic and therapeutic procedures involved.
Abstract: The incidence of burns of the genitalia and peri-anal region which may cause a reconstructive intervention is very low. In the most cases the use of split thickness skin grafts yields a sufficient permanent wound closure. Upcoming problems such as painful scare formation require a reconstructive intervention (Z-plasty, full thickness skin grafting, pedicled flaps etc.). In case that the anal sphincter is involved with the consequence of incontinence or major damage of the genitalia occurred, sophisticated operative solutions are necessary.
Abstract: Carl von Reyher (1846-1890), a young Russian army surgeon of the late nineteenth century, established the principle of repeated debridements on a scientific basis. After a visit to Lister's clinic, acquainting himself with antiseptic wound management, von Reyher was the first to present a controlled study of debridement in contaminated gunshot wounds. He was able to show that the combination of primary debridement and antiseptic treatment decreased the mortality rate of gunshot injuries from 66% to 23%. Although published in more than 16 papers and presented at international congresses, Reyher's contribution was completely negated. Finally more than 30 years later in World War I, the Inter-allied Surgical Conference officially endorsed primary excision with delayed wound closure as the rule for treatment of gunshot wounds.
Abstract: Exposed irradiated joints are characterized by bone and cartilage necrosis with a chronically infected joint space. The indication for treatment results from possible infection spreading and more often because of severe pain. The usual concept of sequential debridement, joint replacement and regional flap coverage, is often impossible due to the radiodermitis and bone necrosis in the neighbourhood of the joint. Even free flaps are associated with a higher failure rate, because of the irradiation of the recipient vessels long vein grafts are often needed. If regional flap coverage is desired, distant flaps with long, not irradiated pedicles must be chosen. Prevention due to special considerations during the first surgery is essential.
Abstract: Tissue damage due to direct contact of liquid propane with the integument is extremely rare. Only five such cases have been described in the literature. We report the case of a girl who sustained a full-thickness skin necrosis of 14.5 % of her body surface area. There is little agreement about the optimal treatment of these injuries in previous reports. The pathophysiological mechanism suggests a freezing injury. The treatment, however, should be analogous to that of third-degree burns.
Abstract: Vascular endothelial growth factor (VEGF) is an important cytokine especially in the process of tumour angiogenesis. A total of 46 soft-tissue sarcomas were analysed for the expression and possible secretion of VEGF by immunohistochemistry, in-situ hybridisation, and enzyme-linked immunosorbent assays (ELISA). VEGF was demonstrated immunohistochemically in tumour tissue in 45 of 46 cases. The detection of mRNA transcripts yielded evidence of synthesis of VEGF in these sarcomas. ELISA could be performed in 21 cases. Higher concentrations of VEGF were found in tumour-related intraoperatively sampled venous blood in 16 out of 21 patients (76%) than in systemic concentrations taken preoperatively. The results indicated the secretion of VEGF by tumour cells although these raised concentrations were not statistically significant. In 12 out of these 16 patients (75%) a concurrent moderate to strong immunoexpression of VEGF was detected. The relevance of VEGF blood concentrations as a potential "progress parameter" for the course of disease remains questionable. This is mainly due to the lack of statistical significance in the difference between systemic VEGF concentrations in patients and those of a control group. Further long-term follow-up studies are needed, which should include patients with tumour recurrences.
Abstract: Growth factors are important substances in the central control of wound healing during the exudative phase. Although these peptides have been applied frequently to chronic wounds in clinical studies, little is known about the naturally occurring levels at the wound site in correlation to healing in superficial wounds. We have therefore investigated the presence of these cytokines in partial thickness wounds. In 16 patients undergoing reconstructive surgery, split-thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5 ml of saline. Chambers placed over unwounded skin served as controls. After 24 hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen at -70 degrees C. Samples were analyzed for protein and growth factors (insulin-like growth factor-1, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3 using a monoclonal Sandwich enzyme-linked immunosorbent assay and radioimmunoassay. All wounds healed in the liquid environment within 7 days (macroscopically) and 11 days (barrier function), respectively. In wound fluid, protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg (unwounded skin), indicating a return of the barrier function. All growth factors could be measured already after 24 hours postwounding. However, the concentrations measured varied from 10 to more than 10,000 pg/ml between the different factors. The highest range was found for insulin-like growth factor-1 (21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3 to 88 pg/ml, respectively). Two different patterns of kinetics were distinguished: (1) a high initial peak decreasing to baseline values or below serum levels by the time of healing (insulin-like growth factor-1, insulin-like growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal growth factor, platelet-derived growth factor-AB, transforming growth factor-beta1) and (2) a low initial concentration followed by an increase to a maximum at the time of epithelialization (interleukin-1alpha, transforming growth factor-beta2). Comparing the growth factor levels measured to serum baseline values, it was found that four of the growth factors appeared in wound fluid at above serum concentrations (interleukin-1alpha, transforming growth factor-beta2, basic fibroblast growth factor, epidermal growth factor); the other factors never reached serum values in wound fluid (insulin-like growth factor, transforming growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the different profiles of secretion might reflect different functions of polypeptide growth factors such as stimulation of epithelialization (epidermal growth factor, insulin-like growth factor-1), matrix synthesis (transforming growth factor-beta), and inflammatory stimulation (interleukin-1alpha). The concentrations determined could serve as guidelines for adapted administration of growth factors once correlations to healing disorders such as overhealing and ulceration are established.
Abstract: Soft tissue sarcomas of the extremities contribute to only 0.9% of all neoplasms. Even in experienced hand radical surgical resection is followed by a recurrency rate of 7 to 35%. The reasons for this high percentage are not yet clear. Since a angiogenesis is a key factor in tumor growth we have investigated concentrations of the angiogenic peptides bFGF, TGF-beta 1, TGF-beta 2 and VEGF in systemic and tumor venous blood of 50 soft tissue sarcoma patients undergoing radical surgical tumor-resection. Systemic blood was obtained preoperatively, during surgery, 1 hour, 1 day and 1 week after surgery. 10cc of venous blood was collected from tumor veins during surgery. Levels of cytokines were measured by Sandwich-ELISA. Preoperative and intraoperative levels were significantly elevated compared to values postoperative. Concentrations of bFGF determined in tumor blood were significantly higher than serum levels but lower than controls obtained from large soft tissue wounds. VEGF and TGF were not elevated.
Abstract: The microenvironment of healing human skin wounds is continuously monitored by a cutaneous chamber model. In recent studies in patients, baseline data for barrier function, temporal profiles of growth factors, and other mediators of healing were established. This model may be useful in clinical research of modulators of healing and wound pharmacology.
Abstract: BACKGROUND AND OBJECTIVE: Despite its practical value, few data exist on assessing the gastrooesophageal junction by transcutaneous sonography (TS). A prospective study was undertaken to compare TS and endoscopy (ES) of this region. PATIENTS AND METHODS: Between 1 September, 1994 and 31 May, 1995 TS of the lower oesophagus was followed by ES of this region in 211 patients (116 women, 95 men; mean age 58.9 [14-90] years). None had previously been examined by ES or radiological contrast study of the oesophagus and stomach. Endoscopist and sonographer were blinded to each other's findings. The ability to visualize the abdominal oesophagus by TS and to recognize abnormalities were compared with ES results, both quantitatively and descriptively. RESULTS: The diaphragmatic course of the terminal oesophagus or (where present) a gastric hernia were well visualized by TS in all 211 patients. In 78 patients with normal results on TS and ES the visible length of the oesophagus was 3.3 +/- 0.8 cm, with a wall thickness of 4.5 +/- 1.0 mm (mean +/- standard deviation). In seven of eight patients with echo-poor wall thickness between 9 and 27 mm, suspected of being malignant, ES revealed neoplasm of the terminal oesophagus or cardia (six T2 to T4 carcinomas; one MALT lymphoma). One patient had involvement of the oesophagus and cardia as part of Crohn's disease. No case of malignancy remained unrecognized by ES. 64 of 77 hiatal hernias diagnosed by ES were also recognized by TS. Hiatal hernia was falsely diagnosed by TS in four patients. Oesophageal varices were correctly identified by TS in three of eight patients, as was one case of achalasia. CONCLUSION: Transcutaneous sonography is a good screening method with a high sensitivity for changes in wall architecture and it provides indications for further selective diagnostic procedures.
Abstract: Over 600 European children have been implanted with Nucleus Mini System 22 Cochlear Implant since 1985. As well as its proven safety und effectiveness it has become increasingly important to monitor the benefit provided postoperatively at regular intervals. The results from 144 European children randomly selected suggest that postlingually deafened children show rapid improvements in performance whilst children deafened before acquisition of speech and language progress at slower but a continuous rate in the first years of experience.
